CFAP53

Chr 18AR

cilia and flagella associated protein 53

NCBI Gene: 220136 ENSG00000172361 UniProt: Q96M91 OMIM: 614759

The CFAP53 protein is a microtubule inner protein component of cilia axonemes that regulates motile cilia beating and is required for both motile and non-motile cilium assembly. Mutations cause visceral heterotaxy-6, a disorder of left-right body asymmetry that typically presents in the neonatal period with complex congenital heart defects and abnormal organ positioning. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189). Regulates motility patterns of both 9+0 and 9+2 motile cilia through differential localization and recruitment of axonemal dynein components (By similarity). Required for centriolar satellite integrity and non-motile cilium assembly (PubMed:26538025). Required for motile cilium formation (PubMed:26538025). Through its role in the beating of primary cilia, involved in the establishment of organ laterality during embryogenesis (PubMed:26531781). Required for sperm flagellum biogenesis and is essential for male fertility (By similarity)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Heterotaxy, visceral, 6, autosomal recessiveMIM #614779

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Heterotaxy, visceral, 6, autosomal recessive; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.34

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.10

OE 0.98 (0.72–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.58Z-score

OE missense 1.10 (1.00–1.21)

300 obs / 273.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.72–1.34)

0≤0.351.4

Missense OE?1.10 (1.00–1.21)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 28 / 28.6Missense obs/exp: 300 / 273.1Syn Z: -0.75

Background carrier burden — how many people carry a rare variant somewhere in CFAP53?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

666 rare PASS variants

Rare truncating (LoF)

1 in 700

147 rare PASS variants

Rare synonymous (reference)

1 in 210

234 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CFAP53. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 780
South Asian	~43k	1 in 88	1 in 490
Remaining (unassigned)	~30k	1 in 69	1 in 580
European (Finnish)	~27k	1 in 400	1 in 2,300
Admixed American	~22k	1 in 82	1 in 480
African / African American	~21k	1 in 50	1 in 570
East Asian	~20k	1 in 89	1 in 940
Ashkenazi Jewish	~13k	1 in 490	1 in 1,300
Middle Eastern	~2,884	1 in 57	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓